Research interests:

fluorinated monosaccharides

antitumour carbohydrate – metallocene conjugates

aziridine derivatives of aldohexoses

including mechanistic aspects of the synthesis and reactivity of these carbohydrate analogues, conformational analysis on the basis of their crystallographic and spectroscopic properties, and application in medicinal chemistry and glycobiology

Fluorinated carbohydratescontinue to attract attention of synthetic chemists and glycobiologists. Introduction of fluorine into carbohydrates modifies their stereoelectronic, lipophilic, steric, and hydrogen-bonding properties. These modifications in turn lead to alterations of their interactions with proteins and other biomolecules or to a greater metabolic stability in comparison with the parent carbohydrates. Fluorinated sugars are used, for example, as probes in studies of enzym – carbohydrate and lectin – carbohydrate interactions, inhibitors of carbohydrate processing enzymes, chemical agents used for modification of the cellular glycome, model compounds for the study of fluorine hydrogen bonding, or components of anticancer vaccines.

Carbohydrate – metallocene conjugates.Metallocenes are organometallic compounds characterized by a transition metal central atom (M) bound to cyclopentadienide (Cp-/C5H5-) ligands, the general formula of metallocenes being Cp2M. Titanocene dichloride was among the first non-platinum organometallics investigated as promising anticancer agents. Although its clinical trials were stopped because of low efficacy and other drawbacks, the last two decades have witnessed renewed research interest in anticancer metallocenes. We have started a programme aimed at improving cytotoxic activity and pharmacological properties of metallocenes by their conjugation to carbohydrates, iminosugars and selected heterocycles. Carbohydrates and iminosugars have typicaly 3 - 6 functional groups that can be modified to ameliorate cytotoxic profile, bioavailability, solubility, biocompatibility, and hydrophobic/hydrophilic balance of the resulting metallocene-carbohydrate conjugate. Recently, we have extended this concept to other organometallic compounds, such as arene ruthenium cationic complexes.

Aziridine derivatives of aldohexoses Aziridines are versatile synthetic intermediates. Important for their utilization in this regard is the cleavage of the three-membered aziridine ring. Cleavage of N-tosylated aziridine ring annelated to a tetrahydropyrane ring of aldohexopyranoses affords interesting analogues of aminosugars which are difficult to prepare otherwise. We studied regio- and stereoselectivity of aziridine ring cleavage fused to the tetrahydropyrane ring of 1,6-anhydro-β-D-hexopyranoses.